The Nidovirales is a recently established order comprising the families Arteriviridae (genus Arterivirus) and Coronaviridae (genera Coronavirus and Torovirus). Despite noteworthy differences in genome size, complexity and virion architecture, coronaviruses, toroviruses and arteriviruses are remarkably similar in genome organization and replication strategy (de Vries, Horzinek et al 1997). The name Nidovirales is derived from the Latin nidus, to nest, and refers to the 3′ coterminal nested set of subgenomic (sg) viral mRNAs produced during infection. Sequence comparisons of the replicase genes suggest that the Nidovirales have evolved from a common ancestor despite their substantial differences.
Coronaviruses cause about 30% of common colds in humans and, unlike rhinoviruses, cause both upper and lower respiratory infections, the latter being a more serious affliction. In addition, coronaviruses cause gastroenteritis and diarrhea in humans and many other serious diseases in non-human animals including mice, chickens, pigs and cats. Although no known human arteriviruses exist, arteriviruses cause a number of diseases in horses, pigs, mice and monkeys.
The most well-known human coronavirus has only recently appeared and is responsible for severe acute respiratory syndrome (SARS), a life threatening form of pneumonia (Peiris, Yuen et al 2003). SARS is caused by a previously unknown coronavirus named SARS coronavirus (SARS-CoV). First appearing in November 2002, an epidemic emerged that spread from its zoonotic origin in Guangdong Province, China, to 26 countries on five continents. By August 2003, a cumulative total of 8422 cases and 774 deaths had been recorded by the World Health Organization. The rapid transmission by aerosols and the fecal-oral route and the high mortality rate (11%) make SARS a potential global threat for which no efficacious therapy is available.
No vaccines for coronaviruses or arteriviruses (Nidoviruses) are available and no effective antiviral therapies are available to treat an infection. As with many other human viral pathogens, available treatment involves supportive measures such as anti-pyretics to keep fever down, fluids, antibiotics for secondary bacterial infections and respiratory support as necessary.
In view of the severity of the diseases caused by Nidoviruses and the lack of effective prevention or therapies, it is therefore an object of the present invention to provide therapeutic compounds and methods for treating a host infected with a coronavirus, torovirus or arterivirus.